The use of drugs such as bromouracil derivatives for enhancing the radiation sensitivity of malignant cells is a potentially useful technique in the treatment of cancer. The aim of this study is to determine the mechanisms of the sensitizing effect. Cryogenic techniques will be used to maintain samples containing sensitizers at low temperature (4.2 degrees K or lower) during X-irradiation, thereby stabilizing the primary stage of the radiation damage process. Electron-nuclear double-resonance (ENDOR) spectroscopy will be used to identify the molecular changes (e.g., oxidation or reduction) induced by ionizing radiation. Subsequent steps in the radiation damage process can be observed on warming the crystal. The emphasis in the forthcoming year's work will be on the step in the radiation chemistry immediately following reduction of the sensitizer molecules by ionization electrons. This step probably involves dissociation of the reduction product. The search for potentially more effective drugs to be used in conjunction with radiation therapy could be expedited by this approach. BIBLIOGRAPHIC REFERENCE: The Reduction of Nucleotides by Ionizing Radiation: Uridine 5' Phosphate and Cytidine 3' Phosphate, H.C. Box, W.R. Potter and E.E. Budzinski, J Chem. Phys. 62, 3476-3478 (1975).